DESCRIPTION: (from abstract) Endophthalmitis, usually resulting from microbial infection of the posterior segment, is a leading blinding complication of common ocular surgeries and globe penetrating injuries. The visual outcome of endophthalmitis varies widely. Factors contributing to the variable visual outcome of endophthalmitis include the manner in which the integrity of the globe was breached (surgery, trauma, bacterial translocation), and the relative virulence of the offending microbe. What constitutes microbial virulence for the eye is still an open question. Studies conducted in the previous period of support highlighted the role of a toxin in contributing to virulence in endophthalmitis. These studies employed a simplified endophthalmitis model to permit unambiguous analysis of variables one at a time. The proposed studies are a logical continuation in that additional variables common to many forms of endophthalmitis are introduced into the model. These variables include the effect of cointroduced blood or leukocytes, the relative fitness of microbes for survival and proliferation in the vitreous (which paradoxically, is inversely related to the fulminance of infection as discussed below), and the relative roles of toxins versus cell wall peptidoglycan in affecting the kinetics and course of disease. Further, the relative ability of currently used antimicrobials to exacerbate inflammation, and the ability of inhibitors of nitric oxide synthesis to preserve vision will be examined.